A novel approach for skin infections: Controlled release topical mats of poly (lactic acid)/poly(ethylene succinate) blends containing Voriconazole

摘要

The oral and injectable formulations of Voriconazole (VRZ), a known antifungal agent with low solubility, seem to cause severe side effects. Consequently, topical application of VRZ could be advantageous for skin fungal infections. In this study, VRZ embedded in a polymeric matrix composed of biocompatible poly(lactic acid) (PLA) and poly(ethylene succinate) (PESu). The mats were prepared via solvent evaporation and fully characterized by Fourier-Transformed Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), in vitro hydrolysis and release studies. The prepared blends defined as immiscible by DSC and SEM while FTIR spectroscopy did not disclose noticeable interactions between the polymers. It was found that hydrolysis was improved by increasing PESu content into the blend. VRZ loaded blends spectra exhibit slight differentiation compared to neat blends while the absence of VRZ melting peak, as DSC illustrated, indicated drug amorphization. Lastly, in vitro release studies depicted a controlled release pattern dependent on mats' hydrolysis degree. An improved antifungal activity of mats was detected by disc diffusion method against various microorganisms. Ex vivo studies of VRZ did not determine high permeation while histopathology results using mice were profitable. The irritation experiments displayed that the mats did not induce any skin irritation.